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Pyridinone compounds

A technology of compounds and compositions, applied in the field of pyridone compounds, can solve problems such as inappropriate expression of HGFR

Active Publication Date: 2012-11-28
BRISTOL MYERS SQUIBB CO
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

In general, most human tumors and tumor cell lines of mesenchymal origin inappropriately express HGFR and / or HGF

Method used

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  • Pyridinone compounds
  • Pyridinone compounds
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Experimental program
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Embodiment 1

[0052] The following abbreviations are used for commonly used reagents: Boc or BOC: tert-butyl carbamate; Fmoc: 9H-fluorenylmethyl carbamate; TEA: triethylamine; NMM: N-methylmorpholine ; Ms, methylsulfonyl; DIEA or DIPEA: diisopropylethylamine or Hunig's base; NMP: N-methylpyrrolidone; BOP reagent: benzotriazol-1-yloxytris(trimethylamino)phosphonium hexafluoro Phosphate; DCC: 1,3-dicyclohexylcarbodiimide; EDCI: 1-(dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride; RT or rt: room temperature; t R : retention time; h, hour (one or more); min: minute (one or more); PyBroP: bromotripyrrolidinylphosphonium hexafluorophosphate; TBTU: O-(1H-benzotriazole-1 -yl)-N, N, N', N'-tetramethyluronium tetrafluoroborate; DMAP: 4-N, N-dimethylaminopyridine; HOBt or HOBT: hydroxybenzotriazole; Na (OAc) 3 BH: sodium triacetoxyborohydride; HOAc: acetic acid; TFA: trifluoroacetic acid; LiHMDS: lithium bis(trimethylsilyl)amide; DMSO: dimethylsulfoxide; MeCN: acetonitrile; MeOH: methanol; Et...

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Abstract

The invention is directed to pyridinone compounds useful for modulating Met kinase, having the following structure: (I) and is further directed to pharmaceutical compositions comprising the compound; and methods for treating proliferative diseases, such as cancer by the administration of this compound.

Description

Background of the invention [0001] Hepatocyte growth factor (HGF), also known as scatter factor (SF), is a mesenchymal-derived cytokine known to induce multiple pleiotropic responses in normal and neoplastic cells due to its ability to interfere with colony formation in vitro ( Sonnenberg et al., J. Cell Biol. 123:223-235, 1993; Matsumato et al., Crit. Rev. Oncog. 3:27-54, 1992; and Stoker et al., Nature 327:239-242, 1987). These responses are known to include proliferation of epithelial and endothelial cells, separation of epithelial colonies into single cells, stimulation of epithelial cell motility (kinesogenic), cell survival, induction of cell morphogenesis (Montesano et al., Cell 67:901-908, 1991 ) and promotion of invasion (Stella et al., Int.J.Biochem.Cell Biol.12:1357-62, 1999 and Stuart et al., Int.J.Exp.Path.81:17-30, 2000), all of which Both are key processes that lead to transfer. HGF has also been reported to promote angiogenesis (Bussolino et al., J. Cell Biol...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07D213/82A61K31/444A61P35/00
CPCC07D213/82A61P35/00A61P43/00A61K31/444
Inventor R·M·波兹莱里G·M·施罗德Z-W·蔡
Owner BRISTOL MYERS SQUIBB CO